Question
Describe the Lac operon model of gene regulation in E. coli as proposed by Jacob and Monod. Explain how the operon is regulated in the presence and absence of lactose.
(NEET 2023, similar pattern)
Solution — Step by Step
The Lac operon in E. coli controls the metabolism of lactose. It consists of:
- Structural genes (z, y, a):
- lacZ: Codes for beta-galactosidase (breaks lactose into glucose + galactose)
- lacY: Codes for permease (transports lactose into the cell)
- lacA: Codes for transacetylase (role in detoxification)
- Promoter (p): Where RNA polymerase binds to start transcription
- Operator (o): The DNA sequence between the promoter and structural genes where the repressor binds
- Regulatory gene (i): Located upstream, codes for the lac repressor protein (produced constitutively)
- The i gene constitutively produces the repressor protein.
- The repressor binds to the operator region.
- This physically blocks RNA polymerase from moving past the promoter to transcribe the structural genes.
- Result: z, y, and a genes are NOT transcribed. No lactose-metabolising enzymes are produced.
The cell saves energy by not making enzymes it does not need.
- Lactose enters the cell and is converted to allolactose (an isomer of lactose).
- Allolactose acts as an inducer — it binds to the repressor protein and changes its shape (allosteric change).
- The altered repressor cannot bind to the operator anymore.
- With the operator free, RNA polymerase can now move past the promoter and transcribe the structural genes (z, y, a) as a single polycistronic mRNA.
- The three enzymes are produced, and lactose is metabolised.
When lactose is used up, no more allolactose is formed. The repressor regains its active shape, binds the operator again, and the operon switches off.
The Lac operon is an inducible operon — it is normally OFF and turned ON by the presence of the substrate (lactose). This is in contrast to repressible operons (like the Trp operon), which are normally ON and turned OFF by the presence of the end product.
Why This Works
The Lac operon is a model of negative regulation — the default state is OFF (repressor blocks transcription), and the inducer removes the block. This is efficient because E. coli does not waste energy producing lactose-digesting enzymes when glucose (a preferred carbon source) is available.
Jacob and Monod received the Nobel Prize in 1965 for this work, which was the first clear demonstration of gene regulation at the transcriptional level.
NEET commonly asks: “What is the role of the inducer in the Lac operon?” Answer: Allolactose (the inducer) binds to the repressor and inactivates it, allowing transcription. Also note: the regulatory gene (i) is NOT part of the operon itself — it is a separate gene that is always expressed.
Advanced detail for competitive exams: the Lac operon also shows positive regulation via the CAP-cAMP system. When glucose is absent, cAMP levels rise, and the CAP-cAMP complex binds near the promoter to enhance RNA polymerase binding. This means the Lac operon is fully active only when lactose is present AND glucose is absent.
Common Mistake
The biggest confusion: students write that “lactose binds to the repressor.” Technically, it is allolactose (an isomer of lactose) that acts as the inducer, not lactose directly. While this distinction may seem minor, NEET has tested it.
Another error: thinking the repressor protein is produced only when needed. The repressor is produced constitutively (always) by the i gene. It is the repressor’s ability to bind the operator that is regulated by allolactose. The i gene does not have an on/off switch — it is always transcribed.